Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection

CD4-Positive T-Lymphocytes Mice, Inbred BALB C Tumor Necrosis Factor-alpha Myocardium Trypanosoma cruzi Adrenalectomy Thymus Gland CD8-Positive T-Lymphocytes Flow Cytometry Parasitemia Animals, Suckling 3. Good health Mice Mifepristone 03 medical and health sciences Receptors, Glucocorticoid 0302 clinical medicine Trypanosomiasis Animals Corticosterone Glucocorticoids
DOI: 10.1677/joe.1.06642 Publication Date: 2006-08-09T17:02:07Z
ABSTRACT
The cytokine-mediated stimulation of the hypothalamus–pituitary–adrenal (HPA) axis is relevant for survival during bacterial endotoxemia and certain viral infections. However, only limited information is available regarding the effects of endogenous glucocorticoids on parasite diseases. We have studied this issue using, as a model, C57Bl/6 and Balb/c mice infected with Trypanosoma cruzi, the causal agent of Chagas’ disease. These two mouse strains differ in the susceptibility to infection with the parasite. An intense stimulation of the HPA-axis was observed 3 weeks after infection in both strains, but glucocorticoid levels were already increased two- to threefold in the less susceptible Balb/c strain during the first week. Blockade of glucocorticoid receptors with the glucocorticoid antagonist RU486, starting on day 10 after infection, partially reversed the thymic atrophy and decreased the number of CD4+CD8+ thymocytes without affecting parasitemia and the number of inflammatory foci in the heart. However, tumor necrosis factor-α blood levels were increased in infected mice of both strains treated with RU486. Furthermore, the blockade of glucocorticoid receptors accelerated death in C57Bl/6J mice and increased lethality to 100% in Balb/c mice. The results obtained represent the first evidence that an endocrine host response that is coupled to the immune process can strongly affect the course of a parasite infection.
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